Studies of the tryptophan synthease alpha 2 beta 2 complex serve as a model for studies of more complicated multienzyme complexes. The identification of active site residues in the beta 2 subunit has been accomplished by use of specific chemical modification. A new affinity label, bromoacetylpyridoxamine phosphate, has been synthesized and shown to react with a specific sulphydryl residue which has also been shown to be essential for catalytic activity by studies with nitrothiocyanobenzoic acid. The location of 3 specifically labeled active site residues in the beta 2 chain is being accomplished by the isolation of protein fragments and peptides. The arrangement of the subunits in the alpha 2 beta 2 complex has been probed by studies of limited proteolysis by trypsin. Subunit association inhibits two types of proteolysis which occur with the separate alpha and beta 2 subunits but does allow the alpha subunit to be cleaved at one region without loss of activity. The active "nicked" alpha subunit has been isolated, denatured, resolved into 2 inactive fragments, and reconstituted. This system is potentially useful for studying folding of the alpha subunit and structure-function relationships.